Superoxide, nitric oxide, and their reaction product, peroxynitrite (ONNO ), have all been shown to independently exert toxic target molecule reactions. Because reactive species are often generated in excess during diverse inflammatory and other pathologic circumstances, we assessed the influence of nitric oxide on membrane lipid peroxidation induced by superoxide, hydrogen peroxide, and hydroxyl radical generation by infusion of either nitric oxide or nitric oxide released from S-nitroso-N-acetyl-penicillamine or S-nitrosoglutathione. Electron spin resonance analysis of incubation mixtures provides no evidence for formation of paramagnetic iron-lipid-nitric oxide complexes in reaction systems. Peroxynitrite-dependent lipid peroxidation, which predominantly occurs by metal-independent mechanisms, was also inhibited by nitric oxide.